Effects of sulfonylurea on the secretion and disposition of insulin and C-peptide.

In an attempt to examine the influence of sulfonylurea on the secretion, disposition and effect of insulin, 9 diabetic patients were studied during three one-month medications with (a) chlorpropamide (t1/2 greater than 24 h) once daily, (b) glipizide (t1/2 2-4 h) once daily, and (c) glipizide in divided dosage. The food intake of each patient was identical during each examination period. Blood concentrations of C-peptide, insulin, glucose, and drugs were determined before and after breakfast and lunch on the 4th day of each examination period. As expected, once-daily administration of glipizide led to higher after-breakfast concentrations of the drug than when the dose was divided. However, the C-peptide changes following breakfast were similar both during these two treatments and also during chlorpropamide, indicating that the amounts of insulin released from the pancreas were equivalent. In spite of this, glipizide once daily yielded 60-70% more insulin in systemic blood following breakfast than did the two other treatments. Reasonably, this signifies that the hepatic extraction of insulin was reduced during once-daily glipizide, allowing more insulin to reach systemic circulation. In addition, this was found to promote a more effective utilization of glucose following breakfast. Following lunch, the C-peptide release, the plasma insulin increase and the blood glucose reduction were greater when glipizide was given in divided dosage than when once-daily glipizide or chlorpropamide was employed. This occurred even though the after-lunch concentration of glipizide in systemic blood was lower rather than higher during divided than during once-daily administration. This supports the notion that the effect of orally administered sulfonylurea is determined not only by its concentration in systemic blood but also by its gastroenterohepatic appearance. Glipizide may offer greater therapeutic flexibility than chlorpropamide, but further studies are required to define the optimum choice and use of sulfonylureas.